Efficacy of gelatin gel sheets in sustaining the release of basic fibroblast growth factor for murine skin defects

Background: Gelatin has been used as a material sustaining the release of basic fibroblast growth factor (bFGF), which promotes fibroblast proliferation and capillary formation and accelerates wound healing. In the application of these materials, bFGF is impregnated immediately before application, and it is difficult to conform the shape to the wound. In this study, we prepared a pliable and plastic gelatin gel sheet (GGS) that sustains bFGF and conforms to the shape of the wound as a result of cross-linking just before application. In addition, we examined the sustained release profile of bFGF from GGS and its effect on wound healing in murine skin defects. Materials and methods: A 13-wt% gelatin solution was mixed with bFGF before cross-linking with 1% glutaraldehyde solution. GGSs impregnated with 7 μg/cm2 of bFGF were incubated in phosphate-buffered saline and collagenase solution, and GGS degradation and bFGF release were evaluated. In the murine experiments, GGSs treated without bFGF and GGSs impregnated with 1, 3.5, 7, or 14 μg/cm2 of bFGF were applied to full-thickness skin defects created on the backs of C57BL/6JJcl mice, and the wound closure, epithelial length, extent of granulation tissue and capillary formation were compared. Results: bFGF was released according to the degradation of GGS in phosphate-buffered saline, and the remaining bFGF was released in collagenase solution. In the animal studies, epithelialization was accelerated in the GGSs treated with 1 and 3.5 μg/cm2 of bFGF, and granulation tissue formation and angiogenesis were promoted based on the amount of bFGF impregnated into the GGS. Conclusions: GGS impregnated with bFGF is capable of sustaining the release of bFGF, with consequent accelerated epithelialization, granulation tissue formation, and angiogenesis in vivo. GGS is a novel and promising wound dressing that sustains bFGF and can be adapted to the shape of various wounds in the treatment of both acute and chronic wounds

Dark Quest. I. Fast and Accurate Emulation of Halo Clustering Statistics and Its Application to Galaxy Clustering

We perform an ensemble of $N$-body simulations with $2048^3$ particles for 101 flat $w$CDM cosmological models sampled based on a maximin-distance Sliced Latin Hypercube Design. By using the halo catalogs extracted at multiple redshifts in the range of $z=[0,1.48]$, we develop Dark Emulator, which enables fast and accurate computations of the halo mass function, halo-matter cross-correlation, and halo auto-correlation as a function of halo masses, redshift, separations and cosmological models, based on the Principal Component Analysis and the Gaussian Process Regression for the large-dimensional input and output data vector. We assess the performance of the emulator using a validation set of $N$-body simulations that are not used in training the emulator. We show that, for typical halos hosting CMASS galaxies in the Sloan Digital Sky Survey, the emulator predicts the halo-matter cross correlation, relevant for galaxy-galaxy weak lensing, with an accuracy better than $2\%$ and the halo auto-correlation, relevant for galaxy clustering correlation, with an accuracy better than $4\%$. We give several demonstrations of the emulator. It can be used to study properties of halo mass density profiles such as the mass-concentration relation and splashback radius for different cosmologies. The emulator outputs can be combined with an analytical prescription of halo-galaxy connection such as the halo occupation distribution at the equation level, instead of using the mock catalogs, to make accurate predictions of galaxy clustering statistics such as the galaxy-galaxy weak lensing and the projected correlation function for any model within the $w$CDM cosmologies, in a few CPU seconds.Comment: 46 pages, 47 figures; version accepted for publication in Ap

Anti-adult T-cell leukemia/lymphoma effects of indole-3-carbinol

<p>Abstract</p> <p>Background</p> <p>Adult T-cell leukemia/lymphoma (ATLL) is a malignancy derived from T cells infected with human T-cell leukemia virus type 1 (HTLV-1), and it is known to be resistant to standard anticancer therapies. Indole-3-carbinol (I3C), a naturally occurring component of <it>Brassica </it>vegetables such as cabbage, broccoli and Brussels sprout, is a promising chemopreventive agent as it is reported to possess antimutagenic, antitumorigenic and antiestrogenic properties in experimental studies. The aim of this study was to determine the potential anti-ATLL effects of I3C both <it>in vitro </it>and <it>in vivo</it>.</p> <p>Results</p> <p>In the <it>in vitro </it>study, I3C inhibited cell viability of HTLV-1-infected T-cell lines and ATLL cells in a dose-dependent manner. Importantly, I3C did not exert any inhibitory effect on uninfected T-cell lines and normal peripheral blood mononuclear cells. I3C prevented the G₁/S transition by reducing the expression of cyclin D1, cyclin D2, Cdk4 and Cdk6, and induced apoptosis by reducing the expression of XIAP, survivin and Bcl-2, and by upregulating the expression of Bak. The induced apoptosis was associated with activation of caspase-3, -8 and -9, and poly(ADP-ribose) polymerase cleavage. I3C also suppressed IκBα phosphorylation and JunD expression, resulting in inactivation of NF-κB and AP-1. Inoculation of HTLV-1-infected T cells in mice with severe combined immunodeficiency resulted in tumor growth. The latter was inhibited by treatment with I3C (50 mg/kg/day orally), but not the vehicle control.</p> <p>Conclusion</p> <p>Our preclinical data suggest that I3C could be potentially a useful chemotherapeutic agent for patients with ATLL.</p

Development of Peer Relationship among Toddlers : An Analysis of the Observations at 18 Months Old

The importance of the peer relationship has been discussed since 1970\u27s, as a part of the development of the infants\u27 social skills to interact with others, which had been almost disregarded for the past 30years. While a great amount of evidence has been provided to support the fact that young infants such as toddlers do interact with peers, some new issues have been coming up. One of them is what condition can facilitate their interaction. In particular, we have received several different points on the role of toys in the interaction of toddlers. We undertook an observational study of young infants to focus on this point. 16 home fostered subjectsin 8pairs at the ages of 18, 21 and 24 months old were observed in the 3 different toy conditions (with no toys, portable toys and non-portable toys) in the playroom free-play situation in 1985-6. Each infant has a same-sex, same-age, unfamiliar peer as its partner. The present paper is our first report of this project. We analysed a part of 18 months olds\u27 data. These were the time-sampled data of the toddlers\u27 peer-oriented behaviors and the minute note records of their interactions. The conditional effects to their behaviors and interactions, especially to their intentions to initiate interactions, were discussed

Estrogen receptor (ER) mRNA expression and molecular subtype distribution in ER-negative/progesterone receptor-positive breast cancers

We examined estrogen receptor (ER) mRNA expression and molecular subtypes in stage I-III breast cancers that are progesterone receptor (PR) positive but ER and HER2 negative by immunohistochemistry (IHC) or fluorescent in situ hybridization. The ER, PR, and HER2 status was determined by IHC as part of routine clinical assessment (N = 501). Gene expression profiling was done with the Affymetrix U133A gene chip. We compared expressions of ESR1 and MKI67 mRNA, distribution of molecular subtypes by the PAM50 classifier, the sensitivity to endocrine therapy index, and the DLDA30 chemotherapy response predictor signature among ER/PR-positive (n = 223), ER-positive/PR-negative (n = 73), ER-negative/PR-positive (n = 20), and triple-negative (n = 185) cancers. All patients received neoadjuvant chemotherapy with an anthracycline and taxane and had adjuvant endocrine therapy only if ER or PR > 10 % positive. ESR1 expression was high in 25 % of ER-negative/PR-positive, in 79 % of ER-positive/PR-negative, in 96 % of ER/PR-positive, and in 12 % of triple-negative cancers by IHC. The average MKI67 expression was significantly higher in the ER-negative/PR-positive and triple-negative cohorts. Among the ER-negative/PR-positive patients, 15 % were luminal A, 5 % were Luminal B, and 65 % were basal like. The relapse-free survival rate of ER-negative/PR-positive patients was equivalent to ER-positive cancers and better than the triple-negative cohort. Only 20-25 % of the ER-negative/PR-positive tumors show molecular features of ER-positive cancers. In this rare subset of patients (i) a second RNA-based assessment may help identifying the minority of ESR1 mRNA-positive, luminal-type cancers and (ii) the safest clinical approach may be to consider both adjuvant endocrine and chemotherapy

Evaluation of platelet reactivity using P2Y12 reaction units in acute coronary syndrome with essential thrombocythemia: A case report

AbstractEssential thrombocythemia (ET) has been reported to cause acute coronary disease. However, the efficacy of anti-platelet therapy for ET is unclear since there are individual differences in the platelet function of ET patients. Here we report a case of a 62-year-old man with ET who was admitted to our hospital because of acute coronary syndrome. He underwent coronary angioplasty. Dual anti-platelet therapy with aspirin (81mg/day) and clopidogrel (75mg/day) was subsequently initiated. We evaluated platelet reactivity in P2Y12 reaction units, and subsequently determined anti-platelet drugs and corresponding doses.<Learning objective: Essential thrombocythemia (ET) is a myeloproliferative disorder that causes acute coronary disease. As there are individual differences in the platelet function of patients with ET, the efficacy of anti-platelet therapy for these patients varies. Evaluation of platelet reactivity using P2Y12 reaction units is useful in determining appropriate anti-platelet drugs and corresponding doses.

Measurement of Language Comprehension by an Adaptive Questionnaire

The purpose of this study is to measure the development of language comprehension of infants, and to construct a multi-stratified adaptive questionnaire by refining the scale presented by Takei and Ogino. The scale presented by Takei and Ogino has so many items that it is laborious to answer all the questions. By employing the adaptive testing method, it was expected to keep the reliability of the questionnaire with considerably fewer items for each mother to answer. Based on this expectation, we made a questionnaire with 6 strata, and administered it to over the 160 mothers who have infants between 3 and 24 months old. The result shows that the reliability of the questionnaire can be kept high with about 1/3 items compared with the original one